Streptococcus mutans is recognized as the etiologic agent in the colonization of the tooth, the formation of plaque, and the induction of dental caries. However, the mechanisms involved in this process is not well established, and controversial results have been reported regarding the identify of virulence factors and the efficiency and safety of the use of some of the S. mutans surface proteins as a dental vaccine. The overall goal of this research is to systematically identify and investigate the structure, function and regulation of S. mutans surface proteins that are invovled in the sucrose-dependent adherence of these organisms, and the use of these determinants as a vaccine to prevent dental caries. The specific aims of this study are to: 1) Identify the surface adherence protein factors in the wall, membrane and culture supernatant of S. mutans and the corresponding determinants expressed by recombinant clones from previously constructed S. mutans gene libraries. 2) Study the structure and genetic organization of these specific surface protein adherence factors. 3) Establish the relationship between their involvement in in vitro sucrose-dependent adherence and in vivo colonization. 4) Investigate the possibility of their regulation by sucrose, and determine if the sucrose-induced active synthesis of dextran is accompanied by an induction of surface protein adherence factors, and/or by a preferential association of these factors with the cell surface instead of excretion into the growth medium. 5) Investigate the use of the cloned adherence protein determinants as a safe and efficient dental vaccine. This study will contribute to understanding and controlling the virulence of S. mutans and other cariogenic bacteria associated with S. mutans in dental plaques. Toward these aims, a multidisciplinary approach will be taken, and advanced methods in biochemistry, microbiology, genetics, immunology, hybridoma and recombinant DNA technology will be used.